GASTRIC HISTAMINE CONTENT AND GASTRIC-ULCER FORMATION IN COLD RESTRAINT STRESSED RATS - EFFECTS OF CINNARIZINE AND FLUNARIZINE

The effects of the calcium channel blockers cinnarizine (20 mg/kg p. o .) and flunarizine (I 0 mg/kg p. o.) on gastric and small intestine hi stamine content and ulcer formation were determined in cold/restraint stressed rats (4-degrees-C for 3 h). The effects of cimetidine (I 00 m g/kg p. o.) were studied for comparison. After the stress, a significa nt increase (+ 27 %) in gastric histamine content concomitant with gas tric ulceration was observed. Pretreatment with cinnarizine or flunari zine restored histamine to the control value and reduced both the inci dence (- 22 % and - 44 % respectively) and the severity (- nearly 35 % ) of gastric ulcers. Neither marked changes in histamine content nor m ucosal lesions were detected in the small intestine. The effects of ci nnarizine and flunarizine resembled those of cimetidine. The obtained data suggest a possible relation between the decrease in the elevated histamine content in stressed rats and the protection against ulcer fo rmation exerted by cinnarizine and flunarizine.